DESCRIPTION (Investigator's Abstract): The hypothesis being tested posits that neuronal hypertrophy, hyperinnervation and rearrangement of neuronal circuits resulting from elevated production of neurotrophic factors by vascular smooth muscle is a critical step in the development and maintenance of hypertension. It is proposed that early changes in blood pressure associated with changes in environment such as increased stress, increased salt intake or weight gain, lead to changes in smooth muscle contractility and proliferation. Changes in intracellular signalling which occur as a result of these events will lead to increased secretion of neurotrophic factors by smooth muscle. Changes in neurotrophic factor supply will lead to alterations in form and function of neurons innervating the vasculature and may cause changes in neuronal circuits extending into the spinal cord and brain. A critical component of this hypothesis is that once formed, these new synapses will be difficult to break and may thus represent a point of no return in the development of hypertension. The proposed experiments will examine trophic interactions between vascular smooth muscle and neurons innervating blood vessels during development of hypertension in Dahl salt-sensitive (SS/Jr) rats, a model of hypertension that has both genetic and environmental components and in rats made hypertensive by treatment with the nitric oxide synthase inhibitor N G-nitro-L-arginine methyl ester (L-NAME), a model of hypertension which has no genetic component. Changes in neurotrophic factor expression will be correlated with changes in sympathetic and sensory innervation of vasculature. The ability of pharmacological manipulations to modify or prevent the changes observed will be investigated. Studies will be performed in vivo and in vitro in cultured smooth muscle. Neurotrophic factor mRNA and protein will be measured using reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immuno assays (ELISA), respectively. Sympathetic and sensory innervation will be examined using histochemical and immunohistochemical techniques. The results will provide information describing trophic interactions between neurons and vascular smooth muscle in hypertensive states.